‘Why is there not something better?’ Teen creates DNA...

1of3Ayush Alag, 17, from Santa Clara, a senior at Harker School, is developing a DNA test to help him battle his food allergies at the Harker School in San Jose on Thursday December 6, 2018.Photo: Cody Glenn / Special To The Chronicle

2of3Ayush Alag, 17, from Santa Clara, a senior at Harker School, is developing a DNA test to help him battle his food allergies at the Harker School in San Jose on Thursday December 6, 2018.Photo: Cody Glenn, Special To The Chronicle

3of3Ayush Alag, 17, from Santa Clara, a senior at Harker School, who is developing a DNA test to help him battle his food allergies, works with his teacher Dr. Eric Nelson at the Harker School in San Jose on Thursday December 6, 2018.Photo: Cody Glenn, Special To The Chronicle

For most of his childhood, Ayush Alag lived with the near-constant fear of a life-threatening allergic reaction.

He had never gone into full anaphylactic shock, but a taste of cashew would make his tongue prickle and his lips swell up. He was convinced that he could die if he accidentally ingested too much.

It wasn’t until middle school that he finally learned — after days of exhaustive testing in his Stanford allergist’s office — that he did not have a severe allergy to cashews or any other foods. He was just sensitive to them. The results were a huge relief, but they made him think: There had to be a better way to diagnose allergies.

So Ayush, at age 14, decided to come up with a better way. After three years of research and development, mostly at his parents’ home in Santa Clara, he created a type of DNA test that could someday be used to quickly identify whether someone has a deadly food allergy or an inconvenient but not life-threatening sensitivity. He has received a grant to further his research — already credited with breaking new ground — and started a company.

“My thinking was, with the technology we have out there, why is there not something better? I’ve always seen science and technology as the golden key,” said Ayush, who is 17 and a senior at the Harker School in San Jose. “I realized this was a really under-researched space in medicine, and that I could really contribute to it.”

Ayush Alag, 17, from Santa Clara, a senior at Harker School, who is developing a DNA test to help him battle his food allergies, works with his teacher Dr. Eric Nelson at the Harker School in San Jose on Thursday December 6, 2018.

Photo: Cody Glenn, Special To The Chronicle

Ayush’s allergy test is a long way from reaching consumers, and it may never work well enough to be of use. But even what he’s accomplished so far is an indicator of the incredible potential lurking in the reams of biological data available to anyone with internet access — and the math skills and fantastically creative mind to use the data.

In simple terms, Ayush’s test looks for genetic markers that a person is allergic — not just sensitive — to certain foods. He developed the test by studying DNA analyses that were already publicly available. With just a laptop, Ayush used those analyses to build an algorithm that sorts out genetic markers associated with allergies.

His work won him first place in a science fair last year, and a few months later, a $10,000 grant from Illumina, a San Diego company focused on genomic testing. Ayush started his company, Allergezy, last March and has brought on several advisers, including his own allergist.

“Ayush has a tremendous amount of initiative and self motivation,” said Dr. Joseph Hernandez, an allergist at Stanford. “He was frustrated because we didn’t have tests that could easily answer his questions about his own allergies.”

Hernandez said that working in Silicon Valley, he’s used to fielding questions from tech-savvy, inquisitive parents — but not typically from his pediatric patients. When Ayush approached him about helping develop the diagnostic tool, Hernandez said he would be happy to participate.

“But I told him I couldn’t help him with the algorithm part of it,” Hernandez said with a laugh. “Most allergists don’t have that kind of training.”

Food allergies are an immune reaction to a protein or chemical found in the particular food. In people with allergies, an antibody called IgE mistakes the protein for an intruder that needs to be wiped out, triggering a flood of histamine, an anti-inflammatory compound. That reaction is what can cause symptoms ranging from a mild rash or upset stomach to anaphylactic shock, which can close off airways.

The simplest and most common tests for food allergies aren’t especially reliable. One is a blood test to check for allergen-specific IgE antibodies. Another is a skin test, during which patients’ skin is pricked with probes laced with a tiny dose of the allergen to see whether they have a reaction.

Both tests often give false positives. Finding IgE in the blood doesn’t mean a patient has a severe allergy. And a reaction to the skin-prick test could mean a patient is sensitive but not fully allergic.

If patients want to know for sure whether they have an allergy — and confirm how severe it is — the “oral food challenge” is considered the most reliable test. That’s what Ayush did, and it was awful.

For one summer, Ayush spent hours almost every week in Hernandez’s office tasting all of the foods, mostly tree nuts, that could hurt him. He’d start with barely a nibble and wait for a reaction, then eat a little more, working his way up to a whole nut. The tests were excruciating: incredibly stressful and mind-numbingly boring at the same time.

“Luckily, I was fine, but it was such a harrowing experience,” Ayush said. “Many kids are too scared to try it.”

Once Ayush learned that he did not have full-blown allergies, he began sampling those foods at home and in restaurants. He’s now able to eat most of the previously off-limits foods in small amounts, and though he sometimes has a physical reaction — the tingling in his mouth, the swollen lips — he knows it won’t get worse than that.

But he was annoyed that he’d gone through years of unnecessary fear and endured the long hours of testing just to get a diagnosis. Ayush, frustrated and always eager to learn, got on his computer to look up everything he could find on allergies and how to test for them.

“He’s always been a very intelligent and analytical kid. And once he starts a problem, you cannot get him to do anything else,” said Ayush’s mother, Alpana Verma-Alag, adding that her son will often skip meals and stay up all night when he’s focused on something.

“It’s hard for a parent, but it’s good as a scientist,” she said. “You have to have that kind of determination.”

As he continued digging into the topic, Ayush found the public data on people with allergies who had undergone genetic sequencing. Such data — stripped of patient-identifying information — is sometimes made public by the researchers who collect it so that other scientists can apply it to their work.

In the data set that Ayush used, the DNA results had been analyzed for changes in gene expression — for example, when certain genes turn off or on. Ayush was able to use those results to build an algorithm that screens for similar gene expressions in any blood sample. He also identified several genes associated with food allergies that no one else had found before.

“I’ve always been research-focused — I was never out to start a company, per se,” Ayush said. “But I think our market potential is really huge. There are 15 million people with food allergies. If we can make a difference in some of their lives, that will be gratifying to me personally.”

He’ll need a much larger sample of DNA tests to refine his algorithm and prove that it’s a reliable diagnostic tool before he can even think about bringing it to the public. Ayush’s next step is doing just that: The grant from Illumina will go toward getting the needed samples and doing genetic sequencing.

He hopes to start that process in February. In March, he has been invited to speak at a symposium of leading scientists in medical big-data analysis.

After that: high school graduation. And, presumably, college — he’s still waiting to find out where he has been accepted.

Erin Allday is a health reporter who writes about infectious diseases, stem cells, neuroscience and consumer health topics like fitness and nutrition. She’s been on the health beat since 2006 (minus a nine-month stint covering Mayor Gavin Newsom). Before joining The Chronicle, Erin worked at newspapers all over the Bay Area and covered a little of everything, including business and technology, city government, and education. She was part of a reporting team that won a Polk Award for regional reporting in 2005, for a series of stories on outsourcing jobs from Santa Rosa to Penang, Malaysia. Erin started her journalism career at the Daily Californian student newspaper and many years later still calls Berkeley her home.